University of Minnesota Medical Center

Although validated prognostic models exist for men with metastatic castration-resistant prostate cancer (mCRPC), current tools do not incorporate genomic biomarkers such as circulating tumor DNA (ctDNA) aneuploidy or pathogenic genetic alterations (PGAs). This study aimed to estimate the prevalence of PGAs in ctDNA, assess their correlation with ctDNA aneuploidy fraction, and evaluate their association with overall survival (OS). Additionally, we developed and validated a clinical-genetic (CG) model to predict OS. We analyzed ctDNA from 776 patients enrolled in the Alliance phase 3 trial (A031201). PGAs were derived using the AR-ctDETECT assay. The net reclassification improvement (NRI) evaluated the added value of the CG model, and the time-dependent area under the receiver operating characteristic curve (tAUC) assessed the accuracy of the OS model. Feature selection using random survival forest identified gains in androgen receptor (AR), AR enhancer, MYC, RSPO2, CCND1, BRAF, and MET; losses or pathogenic variants in ZBTB16, PTEN, MSH6, PPP2R2A, NKX3-1, ZFHX3, TP53, ZNFR3, RB1, FANCA, CHECK1, APC, and CHD1; and a pathogenic AR variant. The CG model significantly outperformed the clinical model, with an average tAUC of 0.77 (95% confidence interval [CI]: 0.73-0.79) for the CG model compared with the tAUC of 0.72 (95% CI: 0.69-0.75, p=0.01) for the clinical model, and NRI of 0.29 between the models. Patients were categorized by the predicted risk scores into poor-, intermediate-, and low-risk groups with median OS of 19.6, 33.6, and 60.8mo, respectively. Incorporation of PGAs from ctDNA into a CG model improved OS prediction by nearly 30% over a clinical model. This model can classify patients into risk groups and is useful for selecting patients in future mCRPC trials.

The Medical College Admissions Test (MCAT) remains a significant barrier for students from low socioeconomic status (SES) backgrounds, with performance disparities driven by unequal access to resources rather than by differences in aptitude. Holistic admissions practices seek to contextualize exam performance alongside other essential pre-medical competencies such as resilience, empathy, and scientific inquiry. Evidence shows that students with middle-tercile MCAT scores who demonstrate these qualities will succeed in medical school and beyond. However, only those who apply can benefit from such holistic review. Little is known about application behaviors at this pivotal stage, when examinees must decide whether to apply with their achieved MCAT score. This study examines the relationship between socioeconomic status, MCAT performance, and application probability. This study analyzed de-identified Association of American Medical Colleges (AAMC) data for all MCAT examinees between 2017 and 2019, including sociodemographic characteristics and total MCAT score. The outcome was allopathic (M.D.) medical school application status through the 2021 application cycle, allowing examinees at least two full years to apply. The AAMC parental education and occupation (EO) indicator stood as a proxy for SES – ranging from EO-1 (less than college degree, any occupation) to EO-5 (doctoral degree; executive, managerial or professional occupations). Socioeconomic disadvantage (SED) was defined as EO-1 and EO-2. Middle- or top-tercile MCAT scores were achieved by 51.8% of examinees with SED (middle, 33.2%; top, 18.6%) compared with 73.1% of examines without SED (middle, 34.4%; top, 38.7%). The probability of applying to medical school was closely tied to MCAT performance, and regardless of SES, the probability of application with any given MCAT score was similar. While most top-tercile performers (92 to 94%) applied, a much lower proportion of middle-tercile performers (78 to 80%) applied. Socioeconomically disadvantaged MCAT examinees infrequently score in the top tercile where application rates are uniformly high. Those with acceptable, middle-tercile performance may under-appreciate their academic achievements through economic adversity, as over 20% do not apply to medical school. Targeted interventions are needed to promote application and maximize the impact of holistic review.

Mental health challenges are a significant concern among students and trainees in medical fields worldwide, including Japan, where high psychological distress is prevalent. This pilot study examined the feasibility and impact of a 6-day creative arts program designed for Japanese medical and international graduate students. A total of 14 students provided informed consent to participate in the study. Employing a convergent mixed-methods design, quantitative and qualitative data were collected and analyzed independently. Students completed the Comprehensive Inventory of Thriving (CIT) before and after the program to assess changes in psychological well-being. Pre-post differences were examined using paired t-tests. Qualitative data collection included post-program surveys, semi-structured interviews, and six-month follow-up interviews. We conducted thematic analysis to identify key patterns in student experiences. We then examined whether changes in CIT scores correlated with the frequency of qualitative codes to identify potential points of convergence between the two datasets. Thirteen students completed all major components of the study, with an average attendance of 5.2 out of 6 sessions. CIT scores significantly increased from before (M = 198.0, SD = 29.9) to after completing the program (M = 217.3, SD = 20.2), t(12) = -4.89, p = .0004, indicating a significant increase in thriving. Thematic analysis yielded three core themes: (1) Discovery through the underexplored parts of self and surroundings, (2) Rapid community bonding through inspiration, and (3) Creativity as a disruption to stress. Six-month follow-up interviews revealed additional themes related to enduring impact from the intervention: Applying creative insights into everyday life and mindsets. Through the convergent mixed-methods analysis, one pairing reached statistical significance: the change over time in the CIT subscore ‘Meaning’ was strongly correlated with the qualitative code “Out of the ordinary” (r = + 0.868), suggesting that increases in participants’ sense of meaning were strongly associated with the frequency of experiences that felt “Out of the ordinary” during the creativity program. The findings suggest that a creative arts program for medical students is both feasible and effective in promoting well-being, enhancing stress management skills, and deepening self-awareness. The program shows promise for integration into medical education to support students’ holistic development and mental health.

As unshaven hair transplantation grows in popularity, terminology has become inconsistent across publications and advertising. This creates confusion for patients and clinicians and undermines informed consent. To map usage, identify confusion sources, and propose definitions for the spectrum of "Unshaven" follicular unit excision (FUE) approaches. The authors performed a structured review of scientific literature, Google Trends for public-facing terms, searches of clinic and media webpages, and standardized prompts to artificial intelligence chatbots. Findings were synthesized into operational definitions and classification. For the FUE procedure, the authors observed overlap, misuse, and conflation of techniques labeled "Unshaven," particularly between partially shaven methods and truly unshaven approaches. Synthesis yielded five categories with explicit procedural boundaries: Shaven FUE, Partially Shaven FUE, Unshaven FUE with pretrimming, Unshaven FUE without pretrimming, and Long-Hair FUE. For each, the authors outline defining steps, patient-visible outcomes, indications, and recommend patient-facing descriptors. The authors propose that 'Shaven' versus 'Unshaven' FUE terminology should be defined exclusively by the donor harvesting technique, irrespective of whether the recipient area is shaved. The proposed standardized nomenclature clarifies FUE categories, improves counseling and expectation-setting, and supports transparent reporting, ethical advertising, and comparability across studies. The authors encourage adoption by clinicians, training programs, and journals.

Gamma delta (γδ) T cells are defined by their unique ability to recognize a limited repertoire of non-peptide, non-major histocompatibility complex-associated antigens on transformed and pathogen-infected cells. In addition to their inability to mediate graft versus host disease, γδ T cells exhibit properties distinct from other lymphocyte subsets, prompting significant interest in their development as an off-the-shelf cellular immunotherapeutic. However, their low abundance in circulation, heterogeneity, limited methods for ex vivo expansion, and under-developed methodologies for genetic modification have hindered basic study and clinical application of γδ T cells. Here, we implement a feeder-free, scalable approach for ex vivo manufacture of polyclonal, non-virally modified, gene-edited chimeric antigen receptor (CAR)-γδ T cells for therapeutic application. Engineered CAR-γδ T cells demonstrate robust functionality in vitro and in vivo. Longitudinal in vivo pharmacokinetic profiling of adoptively transferred polyclonal CAR-γδ T cells uncover subset-specific responses to IL-15 cytokine armoring and multiplex base editing. Our results present a robust platform for genetic modification of polyclonal CAR-γδ T cells and present unique opportunities to further define synergy and the contribution of discrete, engineered CAR-γδ T cell subsets to therapeutic efficacy in vivo.